The long-term objective of the proposed investigation is to determine the effect of 'marijuana usage on syphilis. Since studies of the immunogenic components of the syphilitic treponeme have been progressing rapidly in the past few years, the potential for development of a protective vaccine with which populations at risk of exposure to other persons with syphilis could be immunized is rising. Currently, one of the groups in which the incidence of syphilis is increasing consists of drug abusers. There is more and more evidence that marijuana components are suppressive for the immune response. It is important to determine, therefore, whether or not the immunosuppressive activity of marijuana will prevent users from being able to be immunized successfully by syphilis vaccines. The specfic aims of this project are (1) to measure in the standard rabbit model for human syphilis whether or not delta-9-tetrahydrocannabinol (THC) the active component in marijuana, enhances infectivity of the syphilitic treponemes and (2) to measure whether or not on-going treatment with THC inhibits the induction of protective immunity to syphilis by vaccination. Two-way dose-response experiments will test a range of concentrations of THC against a range of infecting doses of Treponema pallidum subsp. pallidum, the causative agent of syphilis. Optimal effective doses of THC for numbers of infecting organisms will be calculated. For investigation of the effect of THC on immune response to syphilis, the dose-related effect of the drug on active immunization by administration of a vaccine and by previous infection will be determined. The level of protective immunity of rabbits in both cases will be challenged by inoculation of graded doses of treponemes at selected times after THC-treatment is initiated. Results of these experiments will demonstrate whether THC does have an inhibitory effect on host resistance mechanisms to syphilis and the need for additional investigation of the mechanism of action of THC involved.